Induction of sister-chromatid exchanges by chemotherapeutic drugs in spermatogonia of mice: effects of procarbazine, adriamycin, cyclophosphamide and mitomycin C.

The chemotherapeutic drugs procarbazine (PCB), adriamycin (ADR), cyclophosphamide (CP) and mitomycin C (MMC) were evaluated in vivo for induction of sister-chromatid exchanges (SCEs) in differentiating spermatogonia of mice. There was a dose-dependent increase in SCE induced by the drugs. The lowest doses that enhanced the SCE rate to greater than twice baseline frequency were: 10 (PCB), 0.25 (ADR), 5 (CP) and 0.25 (MMC) mg/kg body weight. Based on the x-fold increase in SCE over baseline frequency, induced by the highest test dose (which permitted analysis of SCE), the drugs evaluated were ranked as follows: CP greater than MMC greater than PCB greater than ADR. The persistence of SCE-inducing lesions in spermatogonia was investigated by giving a treatment of CP (20 mg/kg body weight), 6 and 9 days before completion of 5-bromodeoxyuridine (BrdUrd) administration. Within 6-9 days, the SCE rate returned to the baseline level.